Faculty Bibliography

BACKGROUND: The precise relationship between risk factor burden and prevalence of peripheral artery disease (PAD) in different vascular territories (PAD, carotid artery stenosis [CAS], and abdominal aortic aneurysms [AAAs]) is unclear. METHODS: We investigated the association of modifiable risk factors (hypertension, hypercholesterolemia, smoking, diabetes, and sedentary lifestyle) with any and type-specific peripheral vascular disease (PVD) among 3.3 million patients in the U.S., aged 40 to 99, who underwent screening bilateral ankle brachial indices, carotid duplex ultrasound, and abdominal aortic ultrasound in the Life Line Screening program between 2004 and 2008. Multivariate logistic regression analysis was used to estimate the odds of disease in different risk factor categories. Population-attributable risk was calculated to estimate the proportion of disease that could be potentially ascribed to modifiable risk factors. RESULTS: Among 3,319,993 participants, prevalence of any PVD was 7.51% (95% confidence interval [CI], 7.50%-7.53%). PAD was present in 3.56% (95% CI, 3.54%-3.58%), CAS in 3.94% (95% CI, 3.92%-3.96%), and AAAs in 0.88% (95% CI, 0.86%-0.89%). The multivariate-adjusted prevalence with the presence of 0, 1, 2, 3, 4, and 5 modifiable risk factors was 2.76, 4.63, 7.12, 10.73, 16.00, and 22.08 (P < .0001 for trend) for any PVD; 1.18, 2.09, 3.28, 5.14, 8.32, and 12.43 (P < .0001 for trend) for PAD; 1.41, 2.36, 3.72, 5.73, 8.48, and 11.58 (P < .0001 for trend) for CAS; and 0.31, 0.54, 0.85, 1.28, 1.82, and 2.39 (P < .0001 for trend) for AAAs, respectively. These associations were similar for men and women. For every additional modifiable risk factor that was present, the multivariate-adjusted odds of having vascular disease increased significantly (any PVD [odds ratio (OR), 1.58; 95% CI, 1.58-1.59]; PAD [OR, 1.62; 95% CI, 1.62-1.63]; CAS [OR, 1.57; 95% CI, 1.56-1.57]; and AAA [OR, 1.51; 95% CI, 1.50-1.53]). CONCLUSION: This very large contemporary database demonstrates that risk factor burden is associated with an increased prevalence of PVD, and there is a graded association between the number of risk factors present and the prevalence of PAD, CAS, and AAAs.

BACKGROUND: Percutaneous coronary intervention (PCI) of a persistently totally occluded infarct-related artery (IRA) in stable high-risk patients >24h after myocardial infarction (MI) does not reduce the occurrence of death, re-infarction, or heart failure. Diabetic patients are at higher risk for cardiovascular events; we examined their outcomes overall with PCI and optimal medical therapy alone (MED). METHODS: The long-term (7-year) outcomes of 454 diabetic patients (20.6%) randomized to PCI or MED in the Occluded Artery Trial (OAT) were assessed for the composite primary endpoint of death, re-MI, or New York Heart Association class IV heart failure. Diabetics and non-diabetics were compared and outcomes assessed by treatment strategy. RESULTS: The 7-year cumulative primary event rate for diabetic patients was 35.0% vs. 19.4% in the non-diabetic cohort (p<0.001). Multivariable analyses revealed diabetes to be an independent predictor (p<0.01) for the primary outcome, fatal or nonfatal recurrent MI, Class IV Heart Failure (HF), and death. The 7-year cumulative primary event rates were 35.3% in the PCI group vs. 34.5% in the medical therapy group in diabetic patients (p=0.19) and 19.3% in the PCI group vs. 19.5% in the medical therapy group in patients without diabetes (p=0.60). CONCLUSIONS: Despite the higher overall risk conferred by the presence of diabetes, PCI did not improve clinical outcomes in this subpopulation, and is not indicated in otherwise stable patients with a totally occluded infarct-related artery in the sub-acute phase after MI.

BACKGROUND: Plaque rupture, acute ischemia, and necrosis in acute coronary syndromes are accompanied by concurrent pro- and anti-inflammatory cascades. Whether STEMI clinical prediction models can be improved with the addition of baseline inflammatory biomarkers remains unknown. METHODS: In an APEX-AMI trial substudy, 772 patients had a panel of 9 inflammatory serum biomarkers, high sensitivity C reactive protein (hsCRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured at baseline after randomization. Baseline biomarkers were incorporated into a clinical prediction model for a composite of 90-day death, shock, or heart failure. Incremental prognostic value was assessed using Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI). RESULTS: Individually, several biomarkers were independent predictors of clinical outcome: hsCRP (hazard ratio [HR] 1.12; 95% confidence interval [CI], 1.03-1.21; p=0.007, per doubling), NT-proBNP (HR 1.14; 95% CI, 1.06-1.23; p<0.001, per doubling), interleukin (IL)-6 (HR 1.26; 95% CI, 1.12-1.41;p<0.001, per doubling), and inducible protein-10 (IP-10) (HR 0.86; 95% CI, 0.76-0.98; p<0.025, per doubling). The addition of baseline NT-proBNP (NRI 8.6%, p=0.028; IDI 0.030, p<0.001) and IL-6 (NRI 8.8%, p=0.012; IDI 0.036, p<0.001) improved the clinical risk prediction model and the addition of hsCRP (NRI 6.5%, p=0.069; IDI 0.018, p=0.004) yielded minimal improvement. After incorporating NT-proBNP into the model, the remaining biomarkers added little additional predictive value. CONCLUSIONS: Multiple inflammatory biomarkers independently predicted 90-day death, shock or heart failure; however, they added little value to a clinical prediction model that included NT-proBNP. Future studies of inflammatory biomarkers in STEMI should report incremental value in a prediction model that includes NT-proBNP.